"It had a direct toxic effect on cancer cells, and also prevented
angiogenesis – the formation of new blood vessels from pre-existing
ones," said Tom
Li, the study's lead investigator and an associate professor of pharmacy
at Ohio State.

"It's like using one stone to kill two birds."

Li presented the results on August 22 in Philadelphia at the summer
meeting of the American Chemical Society.

OSU 111 is a variation on a theme – Li and his colleagues created
OSU 111 using a known anti-cancer compound, SU-5416, as a model. Although
SU-5416 showed promise in preclinical studies, it did not have the kind
of far-reaching effectiveness that researchers had hoped for.

"One drug with dual
activity means that the body only has to deal with a single compound,
and that could eliminate a lot of complexity in terms of giving
medication to patients, the body's ability to absorb a drug and
also side effects."

But SU-5416 does provide a good blueprint by which researchers can create
dozens of analogs – compounds structurally similar, but with slightly
different chemical compositions.

"We've made close to 50 different analogs by modifying SU-5416,"
Li said.

Laboratory experiments show that OSU 111 is one of the most promising
analogs for killing cancer cells Li's team has found so far. When treated
with OSU 111 in laboratory experiments, the majority of prostate cancer
tissue cells died within three days, Li said.

"This compound stopped cell division in its tracks," he said.

OSU 111 induces apoptosis – cell suicide – in cancer cells
because it keeps key structures called microtubules from working during
cell division. Microtubules distribute chromosomes to new cells. OSU 111
also prevents tumor cells from forming new blood vessels.

Scientists are looking for alternatives to established anti-cancer drugs,
such as Taxol, which is used to kill cancer cells in ovarian, breast and
lung tissue. Drugs like Taxol come from natural sources, and supplies
are sometimes extremely limited. Also, synthetic versions of these drugs
can be very difficult to make.

Providing a drug with more than one effect could also benefit cancer
patients who are inundated with medications.

"Many clinical trials that test new cancer treatments use a combination
of drugs – one to prevent the growth of new blood vessels, for example,
and another to keep cancer cells from dividing and spreading," Li
said. "One drug with dual activity means that the body only has to
deal with a single compound, and that could eliminate a lot of complexity
in terms of giving medication to patients, the body's ability to absorb
a drug and also side effects.

"We want to find a drug with a dual purpose," he continued.
"Angiogenesis is very prominent in many cancers, particularly prostate
cancer. Pure anti-angiogenic compounds haven't been that successful; somehow
cancer cells still find a way to form blood vessels."

Li and his colleagues are continuing to look for even more potent analogs
based on the structure of SU-5416.

"We're developing small, easy-to-make compounds that are similar
to established drugs, but hopefully much easier to come by," he said.